The incidence, risk factors and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia have not been established yet. This study analyzed the clinical and biological characteristics, the impact on prognosis and the cumulative incidence of EMI in a monocentric retrospective study. All consecutive adult pts with a diagnosis of AML observed in our institution between January 2010 and December 2017 were included into the analysis.Overall 346 AMLs were analyzed. The incidence of EMI was 11% (38 pts). The involved sites were: skin (66%), CNS (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most pts (91%) had only one site of EMI, while 9% had multiple sites affected at the same time. Twenty-four (55%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 9 pts (24%); 5 pts had EMI both at presentation and at relapse.EMI had a significantly higher frequency in pts with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), MLL rearrangements (p=0.001), trisomy 8 (p=0,02) and a specific cytofluorimetry pattern (CD117-, p= 0,03; CD56-/CD117-, p= 0,04; CD56+/CD117-, p= 0,04).An analysis regarding treatment, OS and DFS was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient received best supportive care and was consequently excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 pts), hypomethylating agent (5 pts) and low dose citarabine (1 pts); 8 pts (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). Complete remission (CR) rate after induction therapy was 22% with a median DFS of 7.4 months. Median OS of all 27 EMI pts was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI pts who undergone allo-HSCT than those (19 pts) who didn’t receive this procedure (16.7 vs 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for survival in our population (p<0,0001).This study confirms poor prognosis for EMI pts. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in the therapeutic approach of these patients, being associated with a better prognosis.

The treatment of invasive fungal infections has deeply evolved in the last years with the inclusion of new antifungals, mainly new azoles (i.e., posaconazole, isavuconazole), to the therapeutic armamentarium. This review focuses on the role of isavuconazole for treating the most important invasive fungal infections both in animals and humans (hematological and non-hematological patients).

Infections represent one of the most frequent complications during the treatment of patients with Acute Lymphoblastic Leukemia (ALL): of these, almost half develop an infectious event in the majority of cases in induction. The new monoclonal and bispecific antibodies and CAR-T, besides offering new perspectives in the overall survival and disease-free survival of patients, may also transform the epidemiology of infections in ALL by improving the toxicity of treatments. In this review, we examined studies published in the literature over the past 12 years and described the infectious complications of therapy with Blinatumomab, Inotuzumab, Rituximab and CAR-T in adult and pediatric patients with ALL. Infections are less frequent than in traditional chemotherapy treatment with vincristine, corticosteroids and anthracyclines, which has been the backbone of therapy for patients with ALL for years. On the other hand, the infection scenario in the CAR-T setting is quite peculiar: In these patients, infections are more frequent in the first month after infusion and are predominantly bacterial. As the time moves away from day zero, viral infections become more frequent, occurring mainly in patients who have had prolonged cytopenia and major cytokine release syndrome.

Background: Recent studies have indicated that Chinese herbal medicine plays an irreplaceable role in the treatment of leukemia. Mitochondria are the main site of intracellular bio-oxidation and energy metabolism. Regulation of mitochondria to induce leukemia cells apoptosis has become an important target in the treatment of leukemia. However, the mechanism of mitochondrial morphological and functional changes mediating the intervention of traditional Chinese medicine on leukemia cells apoptosis is still unclear. Aims: In our study, we try to show that Hedyotis diffusa can change the mitochondrial morphology by interfering with mitochondrial fusion and fission proteins in KG1a cells, resulting in increased reactive oxygen species (ROS) in mitochondrial matrix, loss of mitochondrial membrane potential, dysfunction of oxidative respiration and energy metabolism, and promoting mitochondrial-related apoptotic factors Cyt-C, Apaf-1, Smac/Diablo and AIF. These changes eventually induce the KG-1a cells apoptosis. Methods: To prove the intervention of Chinese herbal medicine can inhibit the proliferation of leukemia cells in vivo, we established a human acute myeloid leukemia model with NOD/SCID mice and KG-1a cell line as our research platform. The model was randomly divided into experimental group and control group. The expression of mitochondrial apoptotic factors Cyt-C, Apaf-1, Smac/Diablo and AIF in NOD/SCID mice bone marrow was detected by immunohistochemistry. After treatment, the apoptosis rate of leukemia cells derived from the mice in experimental group was significantly increased (P < 0.01), and the expressions of Cyt-C, Apaf-1, Smac/Diablo and AIF in bone marrow were increased (P < 0.05), and the expressions of Cyt-C and Apaf-1 were significantly increased (P < 0.01), compared with control group. And then, we expect to explore the relationship between leukemia cells apoptosis and mitochondrial oxidative respiration and energy metabolism in vitro. Therefore, the water extract of Materia Medica Hedyotis diffusa was used to treat KG-1a cells. After 48 hours, the apoptosis rate and G1 phase arrest rate of KG-1a cells in experimental group were significantly increased in a dose-dependent manner. The morphology, number and distribution of mitochondria were observed by transmission electron microscopy. After treatment, western blot assay showed that the expressions of Cyt-C, Apaf-1, Smac/Diablo and AIF were up-regulated in KG1a cells. ROS was released in large quantities, mitochondrial membrane potential was lost, oxidative respiration and energy metabolism were abnormal, and apoptosis-related factors were released. Finally, we explored the mechanism of mitochondrial morphological and functional changes. After treatment, mitochondrial fusion proteins Mfn-1, Mfn-2, Opa-1 and fission proteins Drp-1, Fis-1, Mff in KG1a cells were detected. Remarkably, the expressions of Mfn-1, Mfn-2, Opa-1 were down-regulated, and Drp-1, Fis-1, Mff were up-regulated. Results: Hedyotis diffusa demonstrated that Hedyotis diffusa could le...